Prematurity Related Ventilatory Control (PRE-VENT) - Specific Aim 2

Prematurity-Related Ventilatory Control (PRE-VENT): Role in Respiratory Outcomes Clinical Research Centers (CRC)

To determine if late (at or beyond postnatal day 14) mild permissive hypercapnia is associated with reduction in apnea, bradycardia, and hypoxemic episodes and with improved stability of oxygenation.

Study Overview

• Status: Completed
• Conditions: Infant,Premature
• Intervention / Treatment: Diagnostic test: Cardiorespiratory monitoring

Detailed Description

Preterm infants who remain intubated or on nasal mechanical ventilation (IMV) at 14 days postnatal age, meet blood gas criteria, have transcutaneous carbondioxide (TcCO2) monitoring with TcCO2 values that trend and correlate appropriately with PaCO2, and are not judged too unstable by Attending neonatologist will qualify.

The investigators will use the data from the 96 hours of intensive multiparametric physiologic monitoring at 2 weeks postnatal age.

The first 24 hours of data collection will be the baseline data. Over the next 72 hours, the investigators will evaluate 3 interventions in a cross-over manner with the initial intervention randomly assigned: Intervention 1 (24-48h of data), Intervention 2 (48-72h of data) and Intervention 3 (72-96h of data).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Regional Neonatal ICU and CCN, University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Inborn infants weighing 401-1,000 grams on admission and/or 22w 0/7d to 28w 6/7d (<29 weeks) inclusive completed weeks of gestation
2. Infants eligible for full care and resuscitation as necessary, and surviving beyond 24 h of age
3. Enrollment in main study protocol (Aim 1 of PreVENT Apnea) at <1 week post-natal age
4. Informed consent from parent/guardian
5. This study will enroll the subset of infants from Aim 1 who are still intubated or on nasal IMV at 2 weeks postnatal age, meet blood gas criteria (arterial or capillary arterialized blood gas values done q12-24h, as most infants do not have an arterial line at 2 weeks: pH >7.25, PaCO2 >40 mm Hg), have TcCO2 monitoring with TcCO2 values that trend and correlate appropriately with PaCO2, and are not judged too unstable by the Attending neonatologist.

Exclusion Criteria:

1. Refusal or withdrawal of consent
2. Major congenital malformations (e.g., not including patent ductus arteriosus, small hernia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher TcCO2; The investigators will evaluate the effects of attempts to increase blood carbon dioxide levels within a narrow range of 5 mm Hg (well within the range of usual clinical practice) in a cross-over manner for 24 hours at a time, over a 4-day period, and use Cardiorespiratory Monitoring to evaluate control of breathing. The investigators will attempt to adjust PCO2 by 5 mm Hg higher from baseline (to max of 70 mm Hg), as long as pH is >7.2. The first 24 hours of the data collection will be the baseline data. Over the next 72 hours, the investigators will evaluate 3 interventions in a cross-over manner, with the initial intervention randomly assigned: Intervention 1 (24-48h of data; Increase TcCO2 by 5 mm Hg), Intervention 2 (48-72h; TcCO2 back to baseline), and Intervention 3 (72-96h; increase TcCO2 again by 5 mm Hg).	Diagnostic test: Cardiorespiratory monitoring; We will use high resolution physiologic monitoring of Heart Rate, Respiratory Rate, Pulse oximetry, (and near-infrared monitoring as well as microcapnography in selected infants) to evaluate control of breathing (apnea, bradycardia, desaturations).
Active Comparator: Lower TcCO2; The investigators will evaluate the effects of attempts to decrease blood carbon dioxide levels within a narrow range of 5 mm Hg (well within the range of usual clinical practice) in a cross-over manner for 24 hours at a time, over a 4-day period, and use Cardiorespiratory Monitoring to evaluate control of breathing. The investigators will attempt to adjust PCO2 by 5 mm Hg lower than baseline (to minimum of 40 mm Hg), as long as pH is <7.45.	Diagnostic test: Cardiorespiratory monitoring; We will use high resolution physiologic monitoring of Heart Rate, Respiratory Rate, Pulse oximetry, (and near-infrared monitoring as well as microcapnography in selected infants) to evaluate control of breathing (apnea, bradycardia, desaturations).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoxemic episode	Hypoxemic episode defined as as oxygen saturation by pulse oximetry (SpO2 )<85% for >10 seconds	During 24 hour time periods with targeted transcutaneous carbondioxide (TcCO2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bradycardic episode	Bradycardic episode defined as heart rate (HR) <100/min for >10 seconds	During 24 hour time periods with targeted TcCO2
Apnea episodes	Apnea defined as Respiratory Rate (RR)=0 for >20 seconds, or RR=0 for >10 seconds + SpO2 <85% or HR <100/min	During 24 hour time periods with targeted TcCO2
Hypoxemic time	Hypoxemic time defined as duration of time with SpO2 <85%	During 24 hour time periods with targeted TcCO2
Bronchopulmonary dysplasia (BPD)	BPD defined using physiologic definition at 36w Post-Menstrual Age (PMA)	36 weeks PMA

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: bradycardia; apnea of prematurity; permissive hypercapnia; hypoxemic episode
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: UAB Neo 017; U01HL133536 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No